中山大学Yi Zhou，Wei Chen和美国哈佛医学院Joseph V. Bonventre共同合作，近期取得重要工作进展。他们研究提出，肠道CXCR6⁺ ILC3通过PD-1表达增强的IL-23受体信号迁移到肾脏并加剧肾纤维化。相关研究成果2024年5月29日在线发表于《免疫学》杂志上。

据介绍，第3组先天性淋巴细胞（ILC3）调节粘膜部位的炎症和组织修复，但这些功能是否与肾脏等其他组织有关尚不清楚。

研究人员观察到人类的肾纤维化与肾脏和血液中ILC3的增加有关。在小鼠中，研究人员发现CXCR6⁺ ILC3从肠粘膜快速迁移，并通过从损伤小管释放的CXCL16在肾脏中积累。在纤维化肾脏中，ILC3增加了程序性细胞死亡-1（PD-1）的表达和随后的IL-17A的产生，以直接激活肌成纤维细胞和纤维化生态位的形成。PD-1的ILC3表达抑制了IL-23R的内吞作用，从而扩增了对ILC3的促纤维化作用至关重要的JAK2/STAT3/RORγt/IL-17A途径。

因此，这一研究揭示了迄今为止未被识别的ILC3从肠道到肾脏的迁移途径，以及ILC3在促进肾纤维化中的PD-1依赖性功能。

附：英文原文

Title: Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression

Author: Zhou Liang, Ziwen Tang, Changjian Zhu, Feng Li, Shuaijiabin Chen, Xu Han, Ruilin Zheng, Xinrong Hu, Ruoni Lin, Qiaoqiao Pei, Changjun Yin, Ji Wang, Ce Tang, Nan Cao, Jincun Zhao, Rong Wang, Xiaoyan Li, Ning Luo, Qiong Wen, Jianwen Yu, Jianbo Li, Xi Xia, Xunhua Zheng, Xin Wang, Naya Huang, Zhong Zhong, Chengqiang Mo, Peisong Chen, Yating Wang, Jinjin Fan, Yun Guo, Haojie Zhong, Jiaqi Liu, Zhenwei Peng, Haiping Mao, Guo-Ping Shi, Joseph V. Bonventre, Wei Chen, Yi Zhou

Issue&Volume: 2024-05-29

Abstract: Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosalsites, but whether these functions pertain to other tissues—like the kidneys—remainsunclear. Here, we observed that renal fibrosis in humans was associated with increasedILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney viaCXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increasedthe expression of programmed cell death-1 (PD-1) and subsequent IL-17A productionto directly activate myofibroblasts and fibrotic niche formation. ILC3 expressionof PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17Apathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveala hitherto unrecognized migration pathway of ILC3s from the intestine to the kidneyand the PD-1-dependent function of ILC3s in promoting renal fibrosis.

DOI: 10.1016/j.immuni.2024.05.004

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00255-3